Beside for intercellular route (Cevc 2004, tang et

Beside SC, tight junction proteins (claudin, occluding and zonula
occludins-1) have been implicated for providing barrier function to skin . Other
than barrier like property of skin outside, there are many factors which affect
the delivery of the drug and they are discussed in the following section. FACTORS AFFECTING NANO BASED




The nanodrugs transdermal delivery is affected by its size and shape which further decide physical steadiness
and their cellular uptake (Escobar Chavez et al 2012). Nanoformulations can be
delivered concurrently using different means/routes owing to their particle
size and physicochemical properties (Borali 2010). Skin anatomical features
only allows free distribution of particles <5-7 nm size through transcellular route (Bouwstra and Ponec 2006, Johnson et al 1997), ?36 nm for intercellular route  (Cevc 2004, tang et al. 2001) and > 3-10 µm for transfollicular route. Particles of smaller size
are preferred since they make available larger surface area hence can have high
drug loading capacity. Attama et al (2007) reported that low particle size solid lipid
nanodispersions  (SLN) are
more stable and well accepted in vivo and active formulkation had high drug
concentration. Maestrelli et al (2009), who investigated ethosomes prepared by different
techniques made similar conclusions and found that small unilamellar vesicles
(SUVs) drug efficacy of benzocaine (BZC) was owing to its small size, higher
surface area which led to more intimate contact with the epithelium for longer
duration of time for therapeutic action. Desai
et al. (2010) and Baroli (2010) concluded that lipophilic nanoparticles have
high partition coefficient and drugs having molecular weight <600 Da are best suited for TDDS. Nanoparticles come in different shapes like spherical, ellipsoidal, triangular, needle shaped, cubic and prism like. They are not always rigid (e.g. lipid particles) and deformable. The shape as well as orientation of the nanoparticles greatly affects their aggregation, penetration route and diffusion coefficient (Baroli 2010). Using newer methods of nanomaterial synthesis, nanoparticles of preferred size and shape for TDDS can be engineered. ZETA POTENTIAL Zeta potential is defines as the number of charges a particle has and particle size distribution and zeta potential of nanoformulations decides the dispersion steadiness of the non-aqueous suspension. SIZE DISTRIBUTION Preparation methods and conditions (like temperature, dispersing medium, stirring rate and viscosity of the organic and aqueous phases) affect the size distribution of nanoparticles formed by different systems. Skin SURFACE PROPERTIES Surface properties of the skin like surface charge and polarity are also key determinants for drug penetration profile in TDDS.  Charges on the skin surface generally influence the ionic interaction of drug molecules with cell membrane, route of penetration and diffusion rate in vivo. Surface charge of the cell membrane is due to presence of negatively charged phosphatidyl choline and sulphated proteoglycans. They are membrane anchored core proteins which are liked to glycosaminoglycan side chains (heparan, dermatan, keratan or chondrotine sulfates) that obtrude from the cell surface. Due to this negative charge in skin at neutral pH, positively charged nano formulations diffuse effectively through skin.  Hoeller et al. (2009) reported effective permeation of drug though porcine skin using phytosphingosine (PS) containing positive charged nanoemulsion than the negatively charged ones.  Generally negatively charged nanoparticles are repelled by cellular membrane, however they are absorbed by non specific process of nanoparticle cluster formation at positive charged sites which lead to neutralization followed by cellular uptake by the process of endocytosis